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Biomedical subjects

P Milner

Publications and source records attributed to P Milner.

106 records · Page 6Linked to original sources
PubMed1986

Vibrotactile stimulation for the adventitiously deaf: an alternative to cochlear implantation.

Acoustic correlates of the prosodic features identifying English contrastive stress, ie, fundamental frequency (Fo), duration and intensity, and listener perceptions were investigated in a profoundly adventitiously deaf subject (D) pre/postvibrotactile stimulation, and in an age-peer normally-hearing person as a control (N). Stimuli were a group of general American English words in which a change of function from noun to verb was associated with a shift of stress from initial to final syllable, eg, CON'test vs conTEST'. Prior to vibrotactile stimulation, D was unable to produce contrastive stress correctly. Only final syllable intensity differences were noted, but proved to be inadequate cues for contrastive stress. Vibrotactile stimulation resulted in changes, specifically significantly higher Fo for initial stressed vs unstressed syllables, significantly louder intensity for final stressed vs unstressed syllables, and significantly longer duration for final stressed vs unstressed syllables. Perceptually, listeners judged D's contrastive stress placement as always occurring on the final syllable previbrotactile stimulation and as 78% correct postvibrotactile stimulation. N's contrastive stress placement was always correct. It was concluded that use of vibrotactile stimulation enhanced D's production and resulted in listeners' perceptions of correct prosody.

Cochlear Implants↗
PubMed1986

Reacquisition of contrastive stress in an adventitiously deaf speaker using a single-channel cochlear implant.

Acoustic correlates of contrastive stress, i.e., fundamental frequency (F0), duration, and intensity, and listener perceptions of stress, were investigated in a profoundly deaf subject (RS) pre/post single-channel cochlear implant and longitudinally, and compared to the overall patterns of age-peer profoundly deaf (JM) and normally hearing subjects (DL). The stimuli were a group of general American English words in which a change of function from noun to verb is associated with a shift of stress from initial to final syllable, e.g., CON'trast versus conTRAST'. Precochlear implant, RS was unable to produce contrastive stress correctly. Hearing one day post-stimulation resulted in significantly higher F0 for initial and final stressed versus unstressed syllables. Four months post-stimulation, RS maintained significantly higher F0 on stressed syllables, as well as generalization of significantly increased intensity and longer syllable duration differences for all stressed versus unstressed syllables. Perceptually, listeners judged RS's contrastive stress placement as incorrect precochlear implant and as always correct post-cochlear implant. JM's contrastive stress was judged as 96% correct, and DL's contrastive stress placement was 100% correct. It was concluded that RS reacquired all acoustic correlates needed for appropriate differentiation of contrastive stress with longitudinal use of the cochlear implant.

Acoustic Stimulation↗
PubMed1985

Enteric nerves in diabetic rats: increase in vasoactive intestinal polypeptide but not substance P.

The distribution of vasoactive intestinal polypeptide (VIP) and substance P-like immunoreactivities was studied by immunohistochemistry in the myenteric plexus and circular muscle layer of the ileum and proximal colon of rats 8 wk after induction of diabetes with streptozotocin. A consistent increase was observed in fluorescence intensity of VIP-like immunoreactivity in the nerve fibers, and intensely stained cell bodies were significantly more frequent in the myenteric plexus of the ileum (p less than 0.001) from diabetic animals. Some varicosities of VIP-like immunoreactive fibers in the myenteric plexus appeared to be enlarged. Vasoactive intestinal polypeptide-like immunoreactivity was increased and VIP-like immunoreactive nerves appeared thicker in the circular muscle layer of both diabetic ileum and proximal colon. The VIP levels were measured biochemically in tissue consisting of the smooth muscle layers and myenteric plexus. A significant increase in the VIP content per centimeter of intestine was found in both the ileum (p less than and proximal colon (p less than 0.01) from diabetic rats. In contrast, no apparent change in substance P innervation was observed immunohistochemically in the myenteric plexus and circular muscle layer of either diabetic ileum or proximal colon when compared with controls. The results are discussed in relation to the symptoms of autonomic neuropathy of the gut in diabetes.

Animals↗
PubMed1984

Effects of thalassemia and microcytosis on the hematologic and vasoocclusive severity of sickle cell anemia.

The characteristic clinical heterogeneity of sickle cell anemia (HbSS) may be, in part, a result of its interactions with alpha-thalassemia. Although alpha-thalassemia clearly affects some hematologic features of HbSS, its role in modulating the vasoocclusive severity of disease is not clear. To further explore this relationship, we examined the incidence of painful episodes, acute chest syndrome, aseptic bone necrosis, and leg ulcers in 3 patient groups with sickle cell disease: (1) 2,147 patients over age 2 yr, stratified according to mean corpuscular volume (MCV); (2) 183 patients selected on the basis of microcytosis and elevated HbA2, on whom globin biosynthesis studies were done; and (3) 125 patients who had alpha-globin genotype assigned by restriction endonuclease gene mapping. When patients were stratified by MCV, there was a reciprocal relationship between HbA2 levels and MCV, reflecting the presence of patients with beta o and alpha-thalassemia in the low MCV groups. The erythrocyte indices and HbA2 levels in patients classified as HbSS-alpha-thalassemia, by either globin synthesis studies or gene mapping, were very similar to those previously reported by others. Neither microcytosis, beta o, or alpha-thalassemia appeared to provide any clear protection from the vasoocclusive complication evaluated, and the prevalence of aseptic necrosis was increased in patients with microcytosis over age 20 yr and in groups with alpha-thalassemia. The effects of a reduced MCV and mean corpuscular hemoglobin concentration (MCHC), of possible benefit by themselves, when accompanied by a reduction in hemolysis and rise in hemoglobin concentration, as in HbSS-alpha-thalassemia, may cause sufficient rise in blood viscosity in critical vascular beds to impair blood flow and negate any amelioration of vasoocclusive complications in HbSS.

Adolescent↗
PubMed1982

Free-field tests of hearing-impaired listeners: early results.

Results are reported from a series of free-field tests of five hearing-impaired listeners. The tests provide relatively crude estimates of listeners' abilities in three types of experiments: free-field masked detection, source angle discrimination (both horizontal and vertical), and identification of source direction. Relations between abilities in the various tasks are noted.

Audiometry↗
PubMed1978

Lateral differences in habituation of ipsilateral head-turning to repeated tactile stimulation in the human newborn.

Lateral differences in habituation of ipsilateral head-turning to repeated tactile perioral stimulation following midline head restriction was studied in 44 full-term neonates. Left-sided stimulation had a significantly greater and faster decremental effect than right-sided stimulation. Even in the absence of tactile stimulation (Control Group), head-turning to the left decreased systematically whereas head-turning to the right did not. The transient efficacy of prior midline head restriction for the elimination of lateral differences in both spontaneous head movements and responsiveness to tactile input suggests that behavioral asymmetry is already well-established in the newborn.

Female↗
PubMed1974

Thalassemias.

Explore the source record for details and available documents.

Erythropoiesis↗
PubMed1973

Hemoglobin Okaloosa (beta 48 (CD7) leucine leads to arginine). An unstable variant with low oxygen affinity.

A slow-moving hemoglobin with electrophoretic mobility similar to that of hemoglobin S was discovered in a white laboratory technologist. She had an elevated reticulocyte count, as did several members of her family. Her red cell survival was shortened. Amino acid analysis indicated that leucine at position beta48 (CD7) had been replaced by arginine. The abnormal hemoglobin, called Okaloosa, was heat-precipitable and had decreased oxygen affinity. It exhibited a greater change in oxygen affinity than hemoglobin A when 2,3 DPG was added to "stripped" hemolysates. These findings cannot be readily explained by current views of structure-function relationships in the hemoglobin molecule. However, it is of interest that the amino acid in position CD7 is normally leucine in the alpha, beta, delta, and gamma-hemoglobin chains and in the myoglobin chain of man and a wide variety of other vertebrates.

Amino Acids↗
PubMedDate not supplied

Neural endothelin in hypertension: increased expression in ganglia and nerves to cerebral arteries of the spontaneously hypertensive rat.

Endothelin has previously been localised in perivascular nerves of the rat basilar artery. Considering its potent vasoconstrictor and mitogenic properties on vascular smooth muscle, the potential role of a neural source of this peptide in hypertension has been investigated. The trigeminal, superior cervical and sphenopalatine ganglia of Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at 16 weeks of age have been examined for immunolocalisation of endothelin at the light and electron microscope level. At the light microscope level, neurones immunopositive for endothelin were detected in these ganglia of the SHR but were not seen in ganglia from WKY rats. This difference was particularly marked in the trigeminal ganglia where endothelin-positive neurones colocalised with substance P immunoreactivity. Using in situ hybridisation techniques, endothelin-1 mRNA was localised to the cytoplasm of neurones in the ganglia and was more prominent in the SHR. At the electron microscope level, endothelin-immunoreactivity was localised at the peripheral perikarya of some neuronal cell bodies of the trigeminal, superior cervical and sphenopalatine ganglia of WKY rats but was more prominent with heavy labelling throughout the cytoplasm of neurones in the SHR. Notably, in the trigeminal ganglia of the SHR only, some endothelin-immunopositive nerve fibres appeared to be damaged and contained vacuoles with granular material. Ultrastructural examination of the basilar artery revealed an increased number of endothelin-positive axons in the SHR, but these axons usually showed selective damage. In summary, in the SHR, there was a marked increase in endothelin particularly in sensory neurones projecting to the basilar artery which also appear to be undergoing degenerative changes. An increased neural source of endothelin in the SHR may contribute to the development of hypertension or may be a consequence of selective degenerative change.

Animals↗
PubMedDate not supplied

Increased shear stress leads to differential release of endothelin and ATP from isolated endothelial cells from 4- and 12-month-old male rabbit aorta.

Freshly isolated thoracic aortic endothelial cells from 4- and 12-month-old male rabbits were exposed to two periods of increased flow rate and the levels of ATP, endothelin (ET) and arginine vasopressin (AVP) released into the perfusate were measured. The rapid, significant release of ATP and ET with increased flow from cells isolated from 12-month-old rabbits was not seen when cells isolated from 4-month-old rabbits were exposed to the same conditions. Increased flow did not stimulate AVP release from cells from either age group. Basal release with low flow also differed in endothelial cells from 4-month-old compared to 12-month-old rabbits; thus in 4-month preparations basal release of AVP was greater, that of ET was smaller, while that of ATP was unchanged relative to 12-month preparations. Immunohistochemical studies showed that almost half as many endothelial cells isolated from 4-month-old rabbits were immunoreactive to ET and AVP compared to cells isolated from 12-month-old animals. It is suggested that the endothelial contribution to the control of vascular tone in rabbit thoracic aorta changes during ageing.

Adenosine Triphosphate↗
PubMedDate not supplied

Long-term guanethidine sympathectomy suppresses flow-induced release of ATP and endothelin from endothelial cells isolated from adult rat aorta.

Chronic rather than acute changes in the autonomic innervation of the vasculature are a feature of ageing and several cardiovascular disorders. To investigate the long-term influence of perivascular innervation on the vascular endothelium, the release of vasoactive substances which have been localized in endothelial cells, namely ATP, endothelin, substance P and vasopressin, was monitored from cells isolated from adult rat thoracic aorta following neonatal guanethidine sympathectomy. The endothelial cells were initially perfused at 0.5 ml/min and exposed to two periods of increased flow at 3.0 ml/min. Cells isolated from control rats released significantly more ATP on both occasions of switching from the lower to higher flow rate and significantly more endothelin on the second exposure to the higher flow rate. In contrast, endothelial cells isolated from sympathectomised rats showed no increased release of either ATP or endothelin with increase flow, although the release of endothelin at the initial flow rate of 0.5 ml/min was higher than in the controls. Substance P and vasopressin levels in the perfusate were the same in controls and after sympathectomy. In summary, long-term sympathectomy suppresses increased flow-induced release of selected vasoactive substances from the endothelium, thus shear-stress-induced changes in local blood flow may be impaired when there are chronic disturbances in the autonomic innervation.

Adenosine Triphosphate↗
PubMedDate not supplied

Neurocompensatory responses to balloon-catheter-induced injury of the rat carotid artery.

Percutaneous transluminal angioplasty relieves discrete arterial stenosis but causes extensive vascular injury. There is denudation of the endothelium and variable medial disruption, but the effect on adventitial structures has not been studied in detail. We have investigated the innervation of the left and right carotid arteries after unilateral balloon-catheter-induced injury. Immunohistochemical examination of the arteries 1 day after Fogarty-catheter-induced injury of the left common carotid artery revealed a reduction in the density of protein gene product 9.5 (PGP)-, substance P (SP)- and calcitonin-gene-related peptide (CGRP)-containing nerves close to the medial smooth muscle of the injured vessel. At the same time, on the side contralateral to the injury, there was a substantial increase in the density of PGP-, SP- and CGRP-containing nerves innervating the carotid artery and vasa vasorum compared to controls. Immunoassay data from these vessels showed a selective increase in SP and CGRP contents of the contralateral carotid artery (SP, controls 0.02 +/- 0.01, operated 0.59 +/- 0.32 pmol/cm; CGRP, controls 0.03 +/- 0.01, operated 0.14 +/- 0.03 pmol/cm, n = 6, p < 0.05). Neuropeptide Y levels were unchanged. Twenty-eight days after surgery, at which time a neointima was present, peptide levels were no different from controls, and the innervation of both the left and right carotid arteries and vasa vasorum was indistinguishable from the controls. In conclusion, balloon-catheter-induced injury includes damage to the perivascular nerves and induces a transient increase in the density of sensory neuropeptide-containing nerves innervating the contralateral, uninjured side. This novel observation may reflect neurocompensatory responses to vascular injury.

Animals↗
PubMedDate not supplied

Interactions between sensory perivascular nerves and the endothelium in brain microvessels.

The purpose of our study was to see if selective denervation of sensory perivascular nerves leads to changes in release of vasoactive substances of endothelial origin from brain microvessels during increased flow. Male rats pups were treated with the neurotoxin, capsaicin, to destroy primary afferent sensory nerves. Three months later, brain microvessels were isolated, placed on a micropore filter and perfused with Krebs buffer. During the course of a 30-min experiment, the flow rate was increased from 0.5 to 3.0 ml/min for two 3-min periods. The levels of ATP, substance P, vasopressin and endothelin in the effluent were measured. Microvessels from 5 rats were pooled for each perfusion experiment. Data from 5 perfusion experiments showed that the release of substance P was significantly higher in the capsaicin-treated rats during the second period of increased flow (3.02 +/- 1.04 pmol/min/mg protein) compared to the vehicle-treated controls (0.30 +/- 0.21 pmol/min/mg protein; p < 0.02). In contrast, the release of ATP at low flow and during the second period of increased flow was significantly lower in the capsaicin-treated rats (0.21 +/- 0.04 compared to 0.50 +/- 0.03 pmol/min/mg protein for controls at low flow, p < 0.001; and 1.19 +/- 0.15 compared to 2.11 +/- 0.26 pmol/min/mg protein for controls during the second period of increased flow, p < 0.01). The release patterns of endothelin and vasopressin were similar in capsaicin-treated and vehicle-treated controls. In conclusion, chronic depletion of sensory innervation leads to altered release of two endothelium-dependent vasodilators, ATP and substance P from the brain microvasculature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Regulation of substance P mRNA expression in human dermal microvascular endothelial cells.

Vascular endothelial cells have been identified as a source of substance P (SP) which may act in an autocrine/paracrine fashion to bring about nitric oxide (NO)-dependent vasodilatation and mitogen-induced cell division or immunologic and inflammatory responses. Whilst SP is localised in and released from endothelial cells, an endothelial mRNA expression of SP has not previously been shown. In the present study, mRNA expression of SP in human dermal microvascular endothelial cells is demonstrated using in situ hybridisation techniques with enhancement procedures. Incubation of microvascular endothelial cells with nerve growth factor (NGF) under conditions of increased shear stress increases the mRNA expression and release of SP Endothelin (ET) release is also enhanced. These changes are pertinent to circulatory, events that may occur in Raynaud's phenomenon in systemic sclerosis.

Cell Culture Techniques↗
PubMedDate not supplied

MR and CT investigation of cerebrovascular disease in sickle cell patients.

Stroke is a common complication of sickle cell disease. Using MR and CT, we studied 10 patients with sickle cell disease and a history of stroke and compared these findings with those of 10 sickle cell patients without stroke. The purpose was to determine if MR could visualize the large vessel vasculopathy previously seen on angiography and to estimate the incidence of asymptomatic abnormalities in the nonstroke group. MR consistently demonstrated the major intracranial arteries and showed three cases with occlusion and three with stenosis of either the internal carotid or middle cerebral arteries. Infarctions were better delineated on MR but were also seen on CT. Seven cases with and two without stroke had high-signal white matter lesions on MR. Further research using cranial MR to develop noninvasive means of identifying sickle cell patients at risk for stroke is warranted.

Adolescent↗